[Federal Register: February 25, 2004 (Volume 69, Number 37)]
[Proposed Rules]
[Page 8600-8604]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25fe04-25]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 870 and 882
[Docket No. 2003N-0567]
Cardiovascular and Neurological Devices; Reclassification of Two
Embolization Devices
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
reclassify two embolization devices to change the names of the devices,
revise the identification of the devices, and reclassify the two
devices from class III (premarket approval) into class II (special
controls). The vascular embolization device (previously the arterial
embolization device) is intended to control hemorrhaging due to
aneurysms, certain tumors, and arteriovenous malformations. The
neurovascular embolization device (previously the artificial
embolization device) is intended to permanently occlude blood flow to
cerebral aneurysms and cerebral arteriovenous malformations. These
reclassifications are being proposed under the agency's own initiative
under the Federal Food, Drug, and Cosmetic Act (the act), as amended by
the Medical Device Amendments of 1976 (the 1976 amendments), the Safe
Medical Devices Act of 1990 (the SMDA), the Food and Drug
Administration Modernization Act of 1997 (FDAMA), and the Medical
Device User Fee and Modernization Act of 2002 (MDUFMA) based on new
information. Elsewhere in this issue of the Federal Register, FDA is
publishing a notice of availability of the draft guidance document that
the agency proposes to use as a special control for these devices.
DATES: Submit written or electronic comments on the proposed rule by
May 25, 2004.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments
.
FOR FURTHER INFORMATION CONTACT: Peter L. Hudson, Center for Devices
and Radiological Health (HFZ-410), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, 301-594-3090.
SUPPLEMENTARY INFORMATION:
I. Regulatory Authorities
The act, as amended by the 1976 amendments (Public Law 94-295), the
SMDA (Public Law 101-629), the FDAMA (Public Law 105-115), and MDUFMA
(Public Law 107-250) established a comprehensive system for the
regulation of medical devices intended for human use. Section 513 of
the act (21 U.S.C. 360c) established three categories (classes) of
devices, depending on the regulatory controls needed to provide
reasonable assurance of their safety and effectiveness. The three
categories of devices are class I (general controls), class II (special
controls), and class III (premarket approval).
Under section 513 of the act, devices that were in commercial
distribution before May 28, 1976 (the date of enactment of the 1976
amendments), generally referred to as preamendments devices, are
classified after FDA has: (1) Received a recommendation from a device
classification panel (an FDA advisory committee); (2) published the
panel's recommendation for comment, along with a proposed regulation
classifying the device; and (3) published a final regulation
classifying the device. FDA has classified most preamendments devices
under these procedures.
Devices that were not in commercial distribution prior to May 28,
1976, generally referred to as postamendments devices, are classified
automatically by statute (section 513(f) of the act) into class III
without any FDA rulemaking process. Postamendments devices require
premarket approval, unless FDA issues an order finding the device to be
[[Page 8601]]
substantially equivalent, in accordance with section 513(i) of the act,
to a predicate device that does not require premarket approval. The
agency determines whether new devices are substantially equivalent to
previously offered devices by means of premarket notification
procedures in section 510(k) of the act (21 U.S.C. 360(k)) and 21 CFR
part 807 of the regulations.
A preamendments device that has been classified into class III may
be marketed, by means of premarket notification procedures, without
submission of a premarket approval application (PMA) until FDA issues a
final regulation under section 515(b) of the act (21 U.S.C. 360e(b))
requiring premarket approval.
In 1990, the SMDA added section 515(i) to the act. This section
requires FDA to issue an order to manufacturers of preamendments class
III devices for which no final regulation requiring the submission of
PMAs has been issued to submit to the agency a summary of, and a
citation to, any information known or otherwise available to them
respecting such devices, including adverse safety and effectiveness
information that has not been submitted under section 519 of the act
(21 U.S.C. 360i). Section 519 of the act requires manufacturers,
importers, and device user facilities to submit adverse event reports
of certain device-related events and reports of certain corrective
actions taken. Section 515(i) of the act also directs FDA to either
revise the classification of the device into class I or class II or
require the device to remain in class III and establish a schedule for
the issuance of a rule requiring the submission of PMAs for those
devices.
In the Federal Register of May 6, 1994 (59 FR 23731), FDA announced
the availability of a document setting forth its strategy for
implementing the provisions of the SMDA that require FDA to review the
classification of preamendments class III devices. Under this plan, the
agency divided preamendments class III devices into the following three
groups: Group 1 devices are devices that FDA believes raise significant
questions of safety and/or effectiveness, but are no longer used or are
in very limited use; group 2 devices are devices that FDA believes have
a high potential for being reclassified into class II; and group 3
devices are devices that FDA believes are currently in commercial
distribution and are not likely candidates for reclassification.
In the Federal Register of August 14, 1995 (60 FR 41984 and 41986),
FDA published two orders for certain class III devices requiring the
submission of safety and effectiveness information in accordance with
the preamendments class III strategy for implementing section 515(i) of
the act. FDA published two updated orders in the Federal Register of
June 13, 1997 (62 FR 32352 and 32355). The orders describe in detail
the format for submitting the type of information required by section
515(i) of the act so that the information submitted would clearly
support reclassification or indicate that a device should be retained
in class III. The orders also scheduled the required submissions in
groups, at 6-month intervals, beginning with August 14, 1996. The
devices proposed in this regulation for reclassification are included
in group 3.
Reclassification of classified preamendments devices is governed by
section 513(e) of the act. This section provides that FDA may, by
rulemaking, reclassify a device (in a proceeding that parallels the
initial classification proceeding) based upon ``new information.'' The
reclassification can be initiated by FDA or by the petition of an
interested person. The term ``new information,'' as used in section
513(e) of the act, includes information developed as a result of a re-
evaluation of the data before the agency when the device was originally
classified, as well as information not presented, not available, or not
developed at that time. (See, e.g., Holland Rantos v. United States
Department of Health, Education, and Welfare, 587 F.2d 1173, 1174 n.1
(D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 (6th Cir. 1970); Bell
v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
Re-evaluation of the data previously before the agency is an
appropriate basis for subsequent regulatory action where the re-
evaluation is made in light of changes in ``medical science.'' (See
Upjohn v. Finch, supra, 422 F.2d at 951.) However, regardless of
whether data before the agency are past or new data, the ``new
information'' upon which reclassification under section 513(3) of the
act is based must consist of ``valid scientific evidence'' as defined
in section 513(a)(3) of the act and 21 CFR 860.7(c)(2). FDA relies upon
``valid scientific evidence'' in the classification process to
determine the level of regulation for devices. For the purpose of
reclassification, the valid scientific evidence upon which the agency
relies must be publicly available. Publicly available information
excludes trade secret and/or confidential commercial information, and
other information that may be protected. (See section 520(c) of the act
(21 U.S.C. 360j(c)).)
II. Regulatory History of the Devices
A. Vascular (Arterial) Embolization Device
In the Federal Register of February 5, 1980 (45 FR 7937), FDA
issued a final rule classifying the arterial embolization device, into
class III (Sec. 870.3300 (21 CFR 870.3300)). The preamble to the
proposed rule to classify the device (44 FR 13363, March 9, 1979)
included the recommendations of the Cardiovascular Device
Classification Panel (the Cardiovascular Panel) regarding the
classification of the device. The Cardiovascular Panel recommended that
the device be classified into class III and identified the following
risks to health associated with the device: Thromboembolization,
inadvertent embolization and infarction, vessel perforation,
progressive granulomatous inflammation, and infection. FDA agreed with
the Cardiovascular Panel's recommendation.
B. Neurovascular (Artificial) Embolization Device
In the Federal Register of September 4, 1979 (44 FR 51777), FDA
issued a final rule classifying the artificial embolization device into
class III (Sec. 882.5950 (21 CFR 882.5950)). The preamble to the
proposed rule to classify the device (43 FR 55730, November 28, 1978)
included the recommendations of the Neurological Devices Classification
Panel (the Neurological Panel), an FDA advisory committee regarding the
classification of the device. The Neurological Panel recommended that
the device be classified into class III and identified tissue
infarction and tissue toxicity as risks to health associated with use
of the device. FDA agreed with the Neurological Panel's recommendation.
III. Device Descriptions
FDA is proposing the following revised device names and
identifications based on the agency's review:
FDA is proposing to rename the arterial embolization device as
``vascular embolization device'' and the artificial embolization device
as the ``neurovascular embolization device.''
A vascular embolization device is an intravascular implant intended
to control hemorrhaging due to aneurysms, certain types of tumors
(e.g., nephroma, hepatoma, uterine fibroids), and arteriovenous
malformations. This does not include cyanoacrylates and other embolic
agents, which act by polymerization or precipitation. Embolization
devices used in neurovascular applications are also not
[[Page 8602]]
included in this classification. (See Sec. 882.5950.)
A neurovascular embolization device is an intravascular implant
intended to permanently occlude blood flow to cerebral aneurysms and
cerebral arteriovenous malformations. This does not include
cyanoacrylates and other embolic agents, which act by polymerization or
precipitation. Embolization devices used in other vascular applications
are also not included in this classification. (See Sec. 870.3300.)
The proposed names of vascular embolization device and
neurovascular embolization device and the proposed device
identifications more accurately reflect the intended uses of the
legally marketed arterial and artificial embolization devices,
respectively. Postamendments class III vascular and neurovascular
embolization devices, such as cyanoacrylates and other embolization
devices, which act by polymerization and precipitation, continue to
require premarket approval.
IV. Recommendation of the Neurological Panel
At a public meeting on June 12, 1998, the Neurological Panel
recommended that the neurovascular (artificial) embolization device be
reclassified from class III into class II (Ref. 1). The Neurological
Panel believed that class II with the special controls, in addition to
the general controls, would reasonably assure the safety and
effectiveness of the device. The Neurological Panel also recommended
that the special controls for the device be labeling, sterilization,
and biocompatibility.
At another public meeting on September 16 and 17, 1999 (Ref. 2),
the Neurological Panel made recommendations on FDA's draft guidance
document entitled ``Guidance Document for Neurological Embolization
Devices.'' The draft guidance document addressed the Neurological
Panel's June 12, 1998, special controls recommendations for the device.
Based on the Neurological Panel's recommendations and public comments
on the draft guidance document, FDA revised the draft guidance document
and issued it on November 1, 2000.
While the Panel's recommendation was specifically for the
neurovascular (artificial) embolization device, because of the
similarity of the vascular (arterial) embolization device to the
neurovascular embolization device, in its intended use, design, risks
to health, controls to mitigate the risks to health, and benefits, FDA
has determined that the Neurological Panel's reclassification
recommendation for the neurovascular embolization device is also
relevant to the vascular embolization device.
V. Risks to Health
After considering the information in one 515(i) submission that
addressed both device classifications (Ref. 3) and two other 515(i)
submissions that addressed the neurovascular embolization device (Refs.
4 and 5), the Neurological Panel's 1998 and 1999 recommendations, as
well as the published literature and Medical Device Reports, FDA has
evaluated the risks to health associated with use of the vascular and
the neurovascular embolization devices. FDA believes that the following
are risks to health associated with use of both device types: Vessel
perforation or rupture, unintended thrombosis, adverse tissue reaction,
infection, and hematoma formation. These risks to health are due to a
combination of factors relating to the severely diseased, damaged, or
malformed blood vessel; clinician experience; and the device.
A. Blood Vessel Perforation or Rupture
Blood vessel perforation or rupture may cause life-threatening
hemorrhage. Blood vessel perforation may result from improper use of
the delivery catheter, device-induced mechanical injury to the
endothelial cells lining the blood vessel, or vasospasm. Blood vessel
perforation or rupture may require surgery to correct this damage.
B. Unintended Thrombosis
Unintended thrombosis from implantation of an embolization device
may cause distal tissue injury (i.e., ischemia and necrosis), which for
the cerebral embolization may cause neurological deficits leading to
cranial nerve palsy, visual impairment, stroke, infarct, unintended
injury to organs, pulmonary embolization, or death. Incorrect device
selection, device misplacement, device migration, device fracture,
inadequate visualization of the device, or use of an inappropriate
catheter delivery system may cause unintended thrombosis.
C. Adverse Tissue Reaction
Adverse tissue reaction is a risk to health common to all implanted
devices. The implantation of embolization devices will elicit a mild
inflammatory reaction typical of a normal foreign body response.
Incompatible materials or impurities in the materials may increase the
severity of a local tissue reaction or cause a systemic tissue
reaction.
D. Infection
Infection of the soft tissue and fever are potential risks to
health associated with all surgical procedures and implanted devices.
Incompatible or impure material composition may irritate the
vasculature, which could increase the risk of infection. Improper
sterilization or packaging may also increase the risk of infection. Use
of a device that is not pyrogen-free may elicit a fever response.
E. Hematoma Formation
Hematoma formation at the delivery catheter entry site, usually
groin access to the femoral artery, is the result of internal bleeding.
VI. Summary of the Reasons for the Reclassification
FDA believes that the vascular embolization device and the
neurovascular embolization device should be reclassified into class II
because special controls, in addition to general controls, provide
reasonable assurance of the safety and effectiveness of the device, and
there is sufficient information to establish special controls to
provide such assurance.
VII. Summary of the Data Upon Which the Reclassification is Based
In addition to the potential risks to health associated with
implantation of the vascular and neurovascular embolization devices
described in section V of this document, there is reasonable knowledge
of the benefits of the devices. Specifically, the vascular and
neurovascular embolization devices may prevent life-threatening
hemorrhage, reduce surgical morbidity and blood loss, and may reduce or
relieve symptoms when surgical resection is not possible.
VIII. Special Controls
FDA believes that the guidance document entitled ``Class II Special
Controls Guidance Document: Vascular and Neurovascular Embolization
Devices'' (the class II special controls guidance document) in addition
to general controls, can address the risks to health described in
section V of this document. Because of the similarity of the two
devices in intended use, design, risks to health, controls to mitigate
the risks to health, and benefits, FDA has determined that the
Neurological Panel's special controls recommendation for the
neurovascular embolization device is also relevant to the vascular
embolization device. Elsewhere in this issue of the Federal Register,
FDA is publishing a notice of availability of this draft class II
special
[[Page 8603]]
controls guidance document that the agency is proposing to use as the
special control for these devices.
The draft guidance document contains specific recommendations with
regard to device performance testing and other information in a
premarket notification (510(k)) submission. Particular sections of the
guidance document address the following topics for both embolization
devices: Preclinical testing (including biocompatibility), sterility,
animal testing, clinical testing, and labeling. In the table 1 of this
document, FDA has identified the risks to health associated with the
use of these devices in the first column and the recommended mitigation
measures identified in the class II special controls guidance document
in the second column. These recommendations will also help ensure that
the device has appropriate performance characteristics and labeling for
its use. Following the effective date of any final reclassification
rule based on this proposal, any firm submitting a 510(k) submission
for these embolization devices will need to address the issues covered
in the class II special controls guidance document. However, the firm
need only show that its device meets the recommendations of the class
II special controls guidance document or in some other way provides
equivalent assurances of safety and effectiveness.
Table 1.--Risks to Health and Recommended Mitigation Measures
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Risk to health Recommended mitigation measures
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Blood vessel perforation or rupture Preclinical testing, Animal
testing, Clinical testing,
Labeling
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Unintended thrombosis Preclinical testing, Animal
testing, Clinical testing,
Labeling
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Adverse tissue reaction Preclinical testing, Animal
testing, Clinical testing
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Infection Sterility
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Hematoma formation Animal testing, Clinical testing,
Labeling
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IX. FDA's Tentative Findings
FDA believes the vascular and the neurovascular embolization
devices should be reclassified into class II because special controls,
in addition to general controls, can provide reasonable assurance of
the safety and effectiveness of the devices and there is sufficient
information to establish special controls to provide such assurance.
FDA, therefore, is proposing to reclassify these devices into class II
and establish the class II special controls guidance document as a
special control for the devices.
For the convenience of the reader, FDA is also adding new Sec.
870.1(e) and Sec. 882.1(e) to inform the reader where to find guidance
documents referenced in parts 870 and 882.
X. Effective Date
FDA proposes that any final rule that may issue based on this
proposal become effective 30 days after its date of publication in the
Federal Register.
XI. Environmental Impact
The agency has determined under 21 CFR 25.34(b) that this proposed
reclassification action is of a type that does not individually or
cumulatively have a significant effect on the human environment.
Therefore, neither an environmental assessment nor an environmental
impact statement is required.
XII. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety and other
advantages; distributive impacts; and equity). The agency believes that
this proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive order. In addition, the proposed
rule is not a significant regulatory action as defined by the Executive
order and so is not subject to review under the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Reclassification of these devices from class III to
class II will relieve all manufacturers of the device types of the
costs of complying with the premarket approval requirements in section
515 of the act. Because reclassification will reduce regulatory costs
with respect to this device, it will impose no significant economic
impact on any small entities, and it may permit small potential
competitors to enter the marketplace by lowering their costs. The
agency therefore certifies that this proposed rule, if finalized, would
not have a significant economic impact on a substantial number of small
entities. In addition, this proposed rule, if finalized, would not
impose costs of $100 million or more on either the private sector or
State, local, and tribal governments in the aggregate, and therefore a
summary statement or analysis under section 202(a) of the Unfunded
Mandates Reform Act of 1995 is not required.
XIII. Paperwork Reduction Act of 1995
This proposed rule does not contain information collection
provisions that are subject to review by the Office of Management and
Budget under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).
XIV. Submission of Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
XV. References
The following references are on display at the Division of Dockets
Management (see ADDRESSES) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday:
1. Neurological Devices Panel, transcript, June 12, 1998, pp. 1-
124.
2. Neurological Devices Panel, transcript, September 17, 1999,
pp. 9-11 and 101-152.
3. 515(i) submission submitted by Target Therapeutics, Inc.,
Fremont, CA, February 12, 1998.
4. 515(i) submission submitted by Cordis Endovascular Corp.,
Miami Lakes, FL, February 13, 1998.
5. 515 (i) submission submitted by Cook, Inc., Bloomington, IN,
February 28, 1998.
List of Subjects in 21 CFR Parts 870 and 882
Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR parts 870 and 882 be amended as follows:
[[Page 8604]]
PART 870--CARDIOVASCULAR DEVICES
1. The authority citation for 21 CFR part 870 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
2. Section 870.1 is amended by adding paragraph (e) to read as
follows:
Sec. 870.1 Scope.
* * * * *
(e) Guidance documents referenced in this part are available on the
Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/guidance.html.
3. Section 870.3300 is revised in subpart D to read as follows:
Sec. 870.3300 Vascular embolization device.
(a) Identification. A vascular embolization device is an
intravascular implant intended to control hemorrhaging due to
aneurysms, certain types of tumors (e.g., nephroma, hepatoma, uterine
fibroids), and arteriovenous malformations. This does not include
cyanoacrylates and other embolic agents, which act by polymerization or
precipitation. Embolization devices used in neurovascular applications
are also not included in this classification. (See 21 CFR 882.5950.)
(b) Classification. Class II (special controls). The special
control for this device is the FDA guidance document entitled ``Class
II Special Controls Guidance Document: Vascular and Neurovascular
Embolization Devices.'' For availability of this guidance document, see
Sec. 870.1(e).
PART 882--NEUROLOGICAL DEVICES
4. The authority citation for 21 CFR part 882 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
5. Section 882.5950 is revised to read as follows:
Sec. 882.5950 Neurovascular embolization device.
(a) Identification. A neurovascular embolization device is an
intravascular implant intended to permanently occlude blood flow to
cerebral aneurysms and cerebral arteriovenous malformations. This does
not include cyanoacrylates and other embolic agents, which act by
polymerization or precipitation. Embolization devices used in other
vascular applications are also not included in this classification, see
Sec. 870.3300.
(b) Classification. Class II (special controls). The special
control for this device is the FDA guidance document entitled ``Class
II Special Controls Guidance Document: Vascular Embolization Devices
and Neurovascular Embolization Devices.'' For availability of this
guidance document, see Sec. 882.1(e).
Dated: February 11, 2004.
Beverly Chernaik Rothstein,
Acting Deputy Director for Policy and Regulations, Center for Devices
and Radiological Health.
[FR Doc. 04-3858 Filed 2-24-04; 8:45 am]
BILLING CODE 4160-01-S